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Research Group: Registry Studies and Clinical Trials II

Research Group Lead

PD Dr. rer. biol. hum. Markus Pfirrmann, Dipl.-Stat., M.Sc.

Staff

Research Areas

Clinical Trials

The group is responsible for overseeing the biostatistics of four currently running clinical trials on Chronic Myeloid Leukemia (CML - the TIGER, DasaHIT-, ENDURE- and FASCINATION trials), one study on multivirus-specific T cell transfer against CMV, EBV, and AdV infections after allogeneic stem cell transplantation (TRACE study), and one study on the secondary prevention of Type 1 Diabetes (Fr1da Study).

Registry Studies

In addition to the above-mentioned clinical trials, data is being collected and analyzed for four registry studies on CML. The registry studies are the NAUT study, the PONTrack study, a CML treatment-free remission registry, and the EURO-SKI study.

Data management using electronic case report forms (eCRFs)

The team began programming eCRFs in 2012 and meanwhile eCRFs have been implemented in seven studies. At current, data on the NAUT, FASCINATION, and PONTrack studies are captured.

Methods, Planning, and Analysis of Registry Studies and Clinical Trials

As part of the biometric support, the research team is responsible for the statistical sections of study protocols. High quality standards are placed on sample size estimation and adjustment methods for tests with multiple hypotheses, as well as the development of analysis methods to ensure a solid methodological basis beyond standard procedures.

Prognostic Factors

A major aim of many projects is, and was, the analysis of potential prognostic factors for various treatment outcomes. The EUTOS registry, for example, provided large data sets of CML patients treated with Imatinib, which led to the development of two widely recognized and valid prognosis systems: The EUTOS score, used to predict the disease remission rate at 18 months (https://www.leukemia-net.org/content/leukemias/cml/eutos_score/index_eng.html)
and the ELTS score for the long-term survival probabilities
(https://www.leukemia-net.org/content/leukemias/cml/elts_score/index_eng.html).
In addition, a prognostic score for AML patients has been proposed (https://www.leukemia-net.org/content/leukemias/aml/aml_prt_score/index_eng.html).
The ELTS score has been independently validated in several countries (Sweden, France, Italy, and China). The ELTS score was recommended as the preferential score by leading international investigators (Hochhaus et al, “European Leukemia Net“ (ELN) recommendations, Leukemia, 2020).

Survival and Competing risk analysis

The primary endpoints of most studies in leukemia research are time-dependent variables. For this reason our research team closely monitors the developments of new methods for the survival analysis of overall survival time, specifically those that account for adjustments for competing risks. As a result our group has authored several publications on the Cox-Cure model, the Fine-Gray model, the modeling of multiple stages, the analysis of left truncated data, and relative survival probabilities.

Currently ongoing studies and projects

  • CML V TIGER study: A prospective, randomized, open-labelled, multicentre clinical trial on the Treatment optimization of newly diagnosed Ph/BCR-ABL positive patients with chronic myeloid leukemia (CML) in chronic phase with nilotinib vs. nilotinib plus interferon alpha induction and nilotinib or interferon alpha maintenance therapy.
  • DasaHIT study: A prospective, randomized, open-labelled, dose-finding study to investigate the tolerability and efficacy to give a medication 5 out of 7 days vs. giving the medication daily.
  • ENDURE study: A prospective, randomized, open-labelled for investigating the efficacy and safety of pegylated proline interferon alpha 2b (AOP2014) in maintaining deep molecular remissions in patients with CML who discontinue ABL-kinase inhibitor therapy - a randomized phase II, multicentre trial with post-study follow-up.
  • FASCINATION study: A prospective, non-randomized, open-labelled multicentre trial with respect to the achievement of deep molecular response with the combination of ATP competing BCR-ABL1 inhibitors with asciminib in newly diagnosed CML patients.
  • TRACE study: A prospective, randomized, double-blind, placebo controlled multicentre trial regarding multivirus-specific T cell transfer against CMV, EBV, and AdV infections after allogeneic stem cell transplantation.
  • Fr1Da study: A Prospective, randomized study to investigate the oral administration of insulin as a secondary prevention for patients with type 1 diabetes.
  • NAUT study: A multicentre, prospective, interventional open label registry after first unsuccessful treatment discontinuation in CML patients estimating the efficacy of nilotinib in inducing the persistence of molecular remission after stopping tyrosine kinase inhibitor (TKI) a 2nd time.
  • PONTrack study: A multicentre, prospective, interventional, open label, uncontrolled registry for the assessment of CML patient status after achievement of deep molecular response with 2 years ponatinib treatment.
  • Treatment-free remission registry for CML patients: A German prospective registry for the documentation of the molecular remission status of CML patients after discontinuation of treatment aiming at identification of prognostic factors for maintenance of molecular remission.
  • EURO-SKI study: A European prospective registry for the documentation of the molecular remission status of CML patients after discontinuation of (mainly) imatinib treatment aiming at identification of prognostic factors for maintenance of molecular remission.